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Multigene Testing of Everyone Diagnosed With Breast Cancer Deemed Cost-Effective, and Researchers Say Policies Should Change

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A study found testing all people diagnosed with breast cancer for mutations in three genes linked to a high risk of the disease — BRCA1, BRCA2, and PALB2 — would be “extremely cost-effective” compared to testing based on family history or clinical guidelines in the United States and the United Kingdom.

The researchers wrote, “These findings support changing current policy to expand genetic testing to all women with [breast cancer].”

The study was published online on Oct. 3, 2019, by JAMA Oncology. Read “A Cost-effectiveness Analysis of Multigene Testing for All Patients With Breast Cancer.”

Gene mutations linked to breast cancer

Three of the most well-known genes that can mutate and raise the risk of breast and/or ovarian cancer are BRCA1, BRCA2, and PALB2. Women who inherit a mutation, or abnormal change, in any of these genes — from their mothers or their fathers — have a much higher-than-average risk of developing breast cancer and/or ovarian cancer. (Abnormal PALB2 genes are suspected to raise the risk of ovarian cancer, but larger studies need to confirm that risk.) Men with these mutations have an increased risk of breast cancer, especially if the BRCA2 gene is affected, and possibly of prostate cancer. Many inherited cases of breast cancer have been associated with mutations in these three genes.

The function of the BRCA and PALB2 genes is to keep breast cells growing normally and prevent any cancer cell growth. But when these genes contain the mutations that are passed from generation to generation, they do not function normally and breast cancer risk increases. Abnormal BRCA1, BRCA2, and PALB2 genes may account for up to 10% of all breast cancers, or 1 out of every 10 cases.

The average woman in the United States has about a 1 in 8, or about 12%, risk of developing breast cancer in her lifetime. Women who have a BRCA1 mutation or BRCA2 mutation (or both) can have up to a 72% risk of being diagnosed with breast cancer during their lifetimes. Breast cancers associated with a BRCA1 or BRCA2 mutation tend to develop in younger women and occur more often in both breasts than cancers in women without these genetic mutations.

Women with a BRCA1 or BRCA2 mutation also have an increased risk of developing ovarian, colon, and pancreatic cancers, as well as melanoma.

Men who have a BRCA2 mutation have a higher risk of breast cancer than men who don't — about 8% by the time they're 80 years old. This is about 80 times greater than average.

Men with a BRCA1 mutation have a slightly higher risk of prostate cancer. Men with a BRCA2 mutation are 7 times more likely than men without the mutation to develop prostate cancer. Other cancer risks, such as cancer of the skin or digestive tract, also may be slightly higher in men with a BRCA1 or BRCA2 mutation.

Preliminary research suggests that a BRCA2 mutation in children and adolescents may be linked to a higher risk of non-Hodgkin lymphoma. Lymphoma is cancer of the lymph system.

Genetic testing

Testing for abnormal breast cancer genes such as BRCA1, BRCA2, and PALB2 is usually done on a blood or saliva sample taken in your doctor’s office and sent to a commercial laboratory or a research testing facility. Most people have it done by a commercial lab. During testing, the genes are separated from the rest of the DNA, and then they are scanned for abnormalities.

Multigene testing, also called panel tests, look at a set of genes for mutations all at once. These tests can include as few as 2 genes, 5 or 6 genes, or as many as 25 to 30 genes — sometimes more. These are sometimes called “next-generation gene sequencing” tests because they use the newest technology to sequence many genes at once.

Why the study was done

Current guidelines in the United States and around the world recommend genetic testing for women diagnosed with breast cancer who meet specific family history and clinical requirements. Still, many people who have a BRCA mutation do not have a strong family history of breast cancer, and other studies have shown that current guidelines miss about 50% of people who have a mutation linked to a high risk of breast cancer.

Knowing that a person diagnosed with breast cancer has a mutation linked to a high risk of the disease can change the person’s treatment options. For example:

  • If a woman is diagnosed with breast cancer in one breast and knows she has a high-risk mutation, she may decide to have the other healthy breast removed — called preventive mastectomy — to reduce the risk of cancer developing in that breast. She also may decide to have her ovaries and fallopian tubes removed preventively to lower the risk of ovarian cancer.
  • If a woman is diagnosed with advanced-stage breast cancer and has a BRCA1 or BRCA2 mutation, the cancer can be treated with a type of medicine called a PARP inhibitor, such as Lynparza (chemical name: olaparib) or Talzenna (chemical name: talazoparib). The poly ADP-ribose polymerase (PARP) enzyme fixes DNA damage in both healthy and cancer cells. PARP inhibitors interfere with the PARP enzyme, making it hard for cancer cells with a BRCA1 or BRCA2 mutation to fix DNA damage. This makes it hard for the cancer cells to survive.

Sharing information about a high-risk mutation also can benefit relatives who haven’t been diagnosed with cancer. These relatives can make lifestyle changes to reduce their risk of cancer, such as exercising regularly and maintaining a healthy weight. They also may opt for more frequent screening. The relatives also may choose to have genetic testing themselves and take more aggressive steps, such as preventive surgery, if they discover they also have a high-risk mutation.

The researchers wanted to analyze the cost of genetic testing for all people diagnosed with breast cancer because they felt that current guidelines were missing important opportunities to prevent breast and ovarian cancer in people who haven’t been diagnosed.

About the study

To do the study, the researchers used information from 11,836 people diagnosed with breast cancer in four large studies.

The researchers used computer models to compare the lifetime costs and effects of panel testing all 11,836 people for mutations in the BRCA1, BRCA2, and PALB2 genes to the lifetime costs and effects of testing only people who meet current genetic testing guidelines for mutations in the BRCA1 and BRCA2 genes.

The researchers measured cost-effectiveness in terms of cost per quality-adjusted life year (QALY). This measurement is difficult to define. Still, the important thing to know is that the standard QALY in the United Kingdom is £30,000 and the standard QALY in the United States is $100,000. So if the QALY for testing all people diagnosed with breast cancer is below those standard figures, testing for all is cost-effective.

Compared to testing based on current genetic testing guidelines, the researchers found that the cost of panel testing for all people diagnosed with breast cancer was:

  • £10,464 per QALY from a payer perspective and £7,216 per QALY from a societal perspective in the United Kingdom
  • $65,661 per QALY from a payer perspective and $61,618 per QALY from a societal perspective in the United States

These costs are well below United Kingdom and United States cost-effectiveness thresholds.

The researchers also found that 1 year’s worth of testing for everyone diagnosed with breast cancer could prevent 2,101 cases of breast and ovarian cancer and 633 deaths in the United Kingdom and 9,733 cases of breast and ovarian cancer and 2,406 deaths in the United States.

“This study found unselected, high-risk multigene testing for all patients with [breast cancer] to be extremely cost-effective compared with testing based on [family history] or clinical criteria for UK and US health systems,” the researchers concluded. “These findings support changing current policy to expand genetic testing to all women with [breast cancer].”

What this means for you

This study adds to evidence supporting expanding the criteria for genetic testing. In August 2019, the U.S. Preventive Services Task Force updated its recommendations on risk assessment, genetic counseling, and genetic testing for BRCA-related cancer, saying that women with either a personal or family history of breast or ovarian cancer, as well as women who are Ashkenazi Jewish (Eastern European), should have their risk assessed by their primary care doctor.

If you have a personal or family history of breast or ovarian cancer or are of Ashkenazi Jewish descent and have never had genetic testing, it makes sense to talk to your doctor about doing a BRCA-related cancer risk assessment and whether genetic testing makes sense for your unique situation.

If you do have a mutation linked to breast cancer and have not been diagnosed, there are lifestyle choices you can make to keep your risk as low as it can be, including:

  • maintaining a healthy weight
  • exercising regularly
  • limiting alcohol
  • never smoking
  • eating a diet rich in unprocessed, nutrient-dense foods (foods that have the most vitamins, minerals, and healthy compounds)

There are also more aggressive steps you can take to reduce your risk of breast cancer, including:

  • more frequent screening that starts at a younger age
  • taking a medicine such as tamoxifen, Evista (chemical name: raloxifene), Aromasin (chemical name: exemestane), or Arimidex (chemical name: anastrozole)
  • removing the healthy breasts and ovaries — called prophylactic or preventive surgery — before cancer develops

For more information on genetic testing, including types of genetic tests and how results are reported, visit the Genetic Testing pages.

For more information on genes and genetic mutations linked to breast cancer, as well as all the risk-lowering steps you can take if you have a genetic mutation, visit the Breast Cancer Risk Factors: Genetics page in the Lower Your Risk section.

To discuss being at high risk for breast cancer with other people, join the Discussion Board forum, High Risk for Breast Cancer. If you've tested positive for a mutation linked to breast cancer and would like to talk about this with others who have also tested positive, join the forum Positive Genetic Test Results.

Written by: Jamie DePolo, senior editor

Reviewed by: Brian Wojciechowski, M.D., medical adviser

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